AntiarthriticsAntiarthritics: In human research, evidence is mixed with respect to the effects of zinc on arthritis symptoms; both benefit and lack of benefit have been shown (164; 156; 429; 430; 655; 160).

AntibioticsAntibiotics: In human research, zinc supplements taken with antibiotics were more effective than antibiotics alone in reducing pain, urinary symptoms, quality of life, and maximum urethra closure pressure for patients with chronic bacterial prostatitis (656). Evidence of benefit is mixed with respect to the effect of zinc on the incidence of infection in children; it may depend on the type of infection (540; 541; 542; 657). Antibacterial effects have been shown in other human and in vitro research (658; 659; 660; 661). According to expert opinion, tetracyclines forms complexes with zinc in the gastrointestinal tract, thereby decreasing the absorption and serum levels of tetracyclines, including demeclocycline, minocycline, and tetracycline (273). However, in human research, doxycycline lacked an interaction with zinc (662; 663). Similarly, quinolones (e.g., ciprofloxacin) may also form complexes with zinc in the gastrointestinal tract and decrease the absorption of these antibiotics (274). According to secondary sources, zinc may decrease the absorption of erythromycin. However, other studies have shown that zinc may increase the efficacy of topical erythromycin. In a study comparing erythromycin with and without added zinc, the results showed a significant reduction in severity and number of acne vulgaris lesions (including inflamed lesions) in the zinc-treated group compared to those taking erythromycin alone (664). Erythromycin has been used in combination formulas with 1.2% zinc for the treatment of acne vulgaris for up to one year (115; 114). Supplementation with zinc in children with shigellosis resulted in an increase in serum shigellacidal antibodies and an increase in circulating CD20+ and CD20+CD38+ cells (257). Zinc has been shown to increase the antienterobacterial activity of Hemidesmus indicus root in vitro (665). Zinc may aid in adjunctive therapy with leprosy treatments (666). According to a systematic review, zinc supplementation resulted in a significant reduction in the number of days of oral antibiotics; effects on the duration of intravenous antibiotic therapy were lacking (352).

Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In humans, zinc demonstrated an effect on platelet aggregation (232). In an in vitro study, zinc inhibited and reversed platelet-activating factor-induced aggregation, and similar inhibitory effects of zinc were observed on serotonin release (233).

AnticonvulsantsAnticonvulsants: In human research, valproate treatment was associated with a reduction in erthryocyte, but not plasma or urinary, levels of zinc (277). The clinical significance of reduced manganese and zinc levels in treated epileptic patients was the topic of discussion (667). Valproate, birth defects, and zinc have also been the topic of discussion (668). Further details are lacking for these two publications.

AntidiabeticsAntidiabetics: In humans, zinc has been reported to improve glycemic control, shown by decreasing HbA1c concentration, as well as decrease fasting and postprandial blood sugar (234). In human research, zinc improved both insulin secretion and insulin sensitivity and exerted insulin-like effects (235). In human research, zinc resulted in improved glucose disappearance and glucose effectiveness in a glucose challenge (236). However, in separate human research, large-dose zinc supplementation induced an elevation of HbA1c (237).

AntihypertensivesAntihypertensives: According to human research, both captopril and enalopril increased renal zinc loss; however, captopril had the greatest effect on increased zinc excretion, and decreased plasma and erythrocyte zinc levels (275). In a patient being treated with captopril, zinc supplementation was able to reverse symptoms of zinc deficiency (676).

Anti-inflammatoriesAnti-inflammatories: In human research, zinc has been shown to decrease C-reactive protein, lipid peroxidation, and inflammatory cytokines, and increase anti-inflammatory proteins A20 and peroxisome proliferator-activated receptor-alpha in elderly patients and in hemodialysis patients (6; 677). Additionally, in human research, zinc acexamate has been shown to be effective and well tolerated for the prevention of NSAID-induced gastroduodenal damage in patients with rheumatic disease (368). Zinc supplementation, with or without other micronutrients (unspecified), in children at risk for zinc deficiency, increased the lymphocyte ratios of CD4(+) to CD8(+) and of CD4(+)CD45RA(+) to CD4(+)CD45RO(+), increased the generation of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), decreased the generation of interleukin-10 (IL-10), and increased plasma interleukin-1 receptor antagonist (sIL-1ra) and soluble tumor necrosis factor receptor-1 (sTNF-R1) (245). Zinc supplementation increased the percentage of phagocytic blood polymorphonuclear cells and the mean phagocytic activity in patients with inflammatory rheumatic disease (678).

AntilipemicsAntilipemics: Zinc had mixed effects on lipid levels in human research. In individuals with low baseline cholesterol levels, zinc resulted in increased total and LDL cholesterol levels and lacked an effect on HDL cholesterol levels (377). In human research, zinc lacked effects on total cholesterol levels, decreased LDL cholesterol, and had mixed effects on HDL cholsterol types, with increased HDL2 and a slight decrease in HDL3 (378). In a separate clinical trial, zinc decreased total cholesterol and lacked effects on triglycerides (171; 379). According to a review, at nontoxic lower levels but still above the RDA (from close to the RDA up to 100-300mg), reported adverse effects included an increased LDL:HDL cholesterol ratio (134), and reduced HDL:total cholesterol ratios were shown in other clinical trials (135). According to reviews, long-term, high-dose administration of zinc may result in decreased HDL cholesterol levels (1). Reduced levels of HDL cholesterol were observed in other clinical trials (137; 138; 136). The mixed effect of zinc on these parameters may be due to dosing, the age, and/or the sex of the participant, as well as baseline zinc and/or plasma lipid levels (379). In animal research, cholestyramine, a bile acid sequestrant, decreased urinary zinc excretion (679). In in vitro research, treatment with HMG-CoA reductase inhibitors resulted in an active zinc signal in peripheral blood mononuclear cells (PBMCs) from low-grade atherosclerotic patients (680).

AntimalarialsAntimalarials: Results are contradictory for the effect of zinc on malaria symptoms (557; 554; 556; 555).

AntineoplasticsAntineoplastics: In human research, patients with head and neck cancers receiving radiotherapy had a better clinical outcome following zinc supplementation compared to those who received placebo (681; 682). Limited benefits were associated with the use of zinc for dysgeusia induced by cancer therapies (340). In human research, cisplatin was shown to increase urinary zinc excretion and reduce plasma zinc levels (276). Zinc increased the cytotoxicity of cisplatin when in the presence of the chelate ethylenediaminetetraacetic acid (EDTA), compared to cisplatin treatment alone (296). Zinc has been studied as an adjunctive therapy to leukemia medication, and side effects have been lacking, other than a slight decrease in granulocyte count (241). In vitro, zinc has been shown to induce apoptosis or inhibit the growth of cancer cells (683; 684).

AntiparasiticsAntiparasitics: Evidence is mixed with respect to the effect of zinc on parasitic infections in human research (150; 148; 487; 486; 561; 685).

AntiretroviralsAntiretrovirals: In human research, zinc offered benefit for some symptoms of HIV, including potentially reducing opportunistic infections and affecting the immune system (261; 190; 259; 260).

AphrodisiacsAphrodisiacs: Results are conflicting with respect to the effects of zinc on sexual function in men on chronic maintenance hemodialysis, according to systematic reviews (432; 431).

CaffeineCaffeine: According to secondary sources, caffeine may decrease zinc concentrations.

Calcium saltsCalcium salts: A decrease in zinc absorption following calcium supplementation has been observed (20); increased calcium levels were observed in children following zinc supplementation (691).

Cognitive agentsCognitive agents: In human research, zinc was of limited usefulness for improving cognition in adolescent girls, and potentially in lead-exposed schoolchildren, although not all available studies agree (497; 693; 499). In adults, zinc had beneficial effects on cognitive function (208). In human research, zinc lacked effects on the psychological functioning of adults with senile dementia (154).

CorticosteroidsCorticosteroids: In human research, large doses or prolonged use of corticosteroids were found to potentially reduce zinc levels, as the pituitary-adrenal axis may play a role in controlling zinc levels (278; 279). Increased urinary excretion of zinc has also been reported (280).

Dermatologic agentsDermatologic agents: In human research, zinc sulfate supplements given to burn victims increased healing in patients whose coefficient units of burned surface (UBS) were greater than 180 (175). In human research, patients with cutaneous leishmaniasis were injected with zinc sulfate intralesionally or took zinc orally, and benefits were noted in some studies (150; 148; 487; 486). In human research, a shampoo containing 1% zinc pyrithione reduced dandruff and PAS-positive microorganisms on the scalp (467), and a zinc shampoo was found effective for tinea versicolor (484; 485). Zinc has also shown benefit for diaper rash (501) and incision wound healing (383; 384; 386). Dermatological effects of zinc have been shown in other human research in terms of sebum excretion (701; 702; 703; 704) and reduced symptoms related to nickel exposure (413).

DexrazoxaneDexrazoxane: In human research, dexrazoxane has been shown to increase zinc excretion (284).

DisulfiramDisulfiram: In animal research, disulfiram has been shown to decrease intestinal absorption of zinc (285). According to expert opinion, disulfiram may act as a chelator of zinc (286).

DiureticsDiuretics: It has been suggested that in humans, thiazide diuretics (e.g., hydrochlorothiazide) and thiazide-like diuretics (e.g., chlorthalidone) may increase the urinary excretion of zinc (287; 288; 289; 290). In human research, hydrochlorothiazide increased urinary zinc excretion (291). Loop diuretics (e.g., furosemide) have been shown to reduce zinc concentrations and increase zinc excretion to a lesser extent than thiazide diuretics (287). However, in human research, the potassium-sparing diuretic amiloride (Midamor®) was also shown to reduce urinary zinc excretion (292). In other research, administration of diuretics lacked an effect on serum zinc levels (705).

Drugs used for osteoporosisDrugs used for osteoporosis: Zinc supplementation in healthy male subjects increased total alkaline phosphatase activity (ALP), bone-specific alkaline phosphatase activity (BAP-E), and BAP mass (BAP-M), markers of bone turnover; however, effects on parameters of bone resorption were lacking (706; 338; 489; 162). Supplementation also increased the urinary excretion of N-telopeptides and decreased serum calcitonin levels. During consumption of a diet low in copper, plasma osteocalcin was higher during low intake of zinc compared to high intake.

EthambutolEthambutol: Campbell et al. wrote a letter regarding ethambutol and the eye in relation to both zinc and copper levels (further details are lacking) (707). In a separate study, it was determined that in patients with lower plasma zinc levels, optic neuropathy increased in patients treated with ethambutol (708).

FluoroquinolonesFluoroquinolones: According to a review, zinc reduces the availability of fluoroquinolones (294), and the possible interaction between fluoroquinolones and zinc was discussed by other authors (136).

Hormonal agentsHormonal agents: In human research, estrogens have been shown to reduce zinc excretion (716; 717) and plasma zinc levels (308); however, effects on plasma zinc levels were lacking in some studies (718; 719). In human research, zinc increased serum testosterone and dihydrotestosterone levels in most, but not all, studies, while effects on LH, FSH, and prolactin were lacking in most, but not all, studies (436; 391; 709; 431; 720; 489; 390; 431; 721; 387). In further human research, hormonal effects of zinc have included increased serum insulin-like growth factor I (IGF-I) concentrations (722), and there were positive correlations with IGF binding protein-3 (IGFBP-3) levels (723). In animal research, zinc showed importance for gonadal growth and pituitary synthesis of gonadotropins (724). According to a review, although use of oral contraceptives may reduce circulating zinc levels, some tissue levels may be increased, and evidence in support of an increased zinc requirement is lacking (725).

ImmunosuppressantsImmunosuppressants: In human research, zinc offered benefit to the immune system in the elderly (238; 239; 259), hemodialysis patients (256), children or young adults (240; 241), and healthy adult males (242). In human research, zinc, with or without other nutrients, affected levels of various types of T cells and other immune cells, affected levels of various cytokines, and modulated the innate immune system (243; 244; 245; 246; 247; 248; 249; 250; 251; 252; 241; 253; 255; 254; 238; 239; 256; 240; 257; 258; 259; 260; 261). Similar effects, as well as other immune modifying effects, have been shown in laboratory studies (262; 263). In another study, it was determined that zinc supplementation lacked a long-lasting effect on immune status in healthy adults (262). According to expert opinion, long-term, high-dose administration of zinc may result in suppressed immunity (1). According to a review, long-term, high-dose administration of zinc may result in suppressed immunity (1; 136). Reduced immune responses (phytohemagglutinin challenge, chemotaxis) were observed in a small study in which volunteers received 300mg of zinc daily for six weeks (264).

Penicillamine (Cuprimine®)Penicillamine (Cuprimine®): In human and in vitro research, penicillamine chelated zinc and was therefore suggested to reduce its supplemental effects (296; 202). Dosing times should be separated by at least two hours. Seelig et al. suggested the potential for a role of zinc depletion in autoimmune complications of penicillamine (further details are lacking) (732), and the possible interaction between penicillamine and zinc was discussed by other authors (136).

PhenytoinPhenytoin: In human research, phenytoin use has been associated with reduced zinc levels (297). In human research and according to expert opinion, phenytoin acted as a chelator of zinc (297; 286).

PropofolPropofol: Propofol in fusion contains EDTA, a chelator of zinc. In human research, concurrent use increased the urinary excretion of zinc and reduce zinc levels (298).

Respiratory agentsRespiratory agents: Evidence is mixed with respect to the effect of zinc on the degree of respiratory illness, as shown in meta-analyses and systematic reviews (194; 553; 669; 734; 551). Evidence is mixed with respect to the effect of zinc on pneumonia (512; 192; 215; 214; 552; 547; 735).

TrientineTrientine: According to secondary sources, there was a lack of an interaction between zinc acetate and trientine in the treatment of Wilson's disease, and the possible interaction between trientine and zinc was discussed by other authors (136).

VaccinesVaccines: In human research, the antibody response to the vaccine increased with zinc treatment (256).

Wound-healing agentsWound-healing agents: Supplementation with an antioxidant mixture consisting of vitamin E, vitamin C, and zinc, in burned children, resulted in a lower time to heal (740). A dressing containing zinc, in combination with calcium and manganese, has been shown to stimulate proliferation, growth, collagen I and III synthesis, and the migration of fibroblasts (741).

ZidovudineZidovudine: According to secondary sources, zidovudine may play a role in reducing zinc levels in individuals with AIDS. In human research, zinc supplementation as an adjunct to zidovudine therapy in AIDS patients appeared to restrict opportunistic infections caused by Pneumocystis carinii and Candida, but not cytomegalovirus or toxoplasma infections (260).

Acne herbs and supplementsAcne herbs and supplements: In human research, topical or systemic use of zinc was shown in most, but not all, studies to result in significant improvements in the acne condition (145; 157; 331; 172; 163; 329; 332; 159; 143; 139; 330; 152; 333; 654; 179).

AnalgesicsAnalgesics: In psoriasis patients, use of zinc resulted in a decreased need for analgesics (424).

AntiarthriticsAntiarthritics: In human research, evidence is mixed with respect to the effects of zinc on arthritis symptoms; both benefit and lack of benefit have been shown (164; 156; 429; 430; 655; 160).

AntibacterialsAntibacterials: In human research, zinc supplements taken with antibiotics were more effective than antibiotics alone in reducing pain, urinary symptoms, quality of life, and maximum urethra closure pressure for patients with chronic bacterial prostatitis (656). Evidence of benefit is mixed with respect to the effect of zinc on the incidence of infection in children; it may depend on the type of infection (540; 541; 542; 657). Antibacterial effects have been shown in other human and in vitro research (658; 659; 660; 661). According to expert opinion, tetracyclines forms complexes with zinc in the gastrointestinal tract, thereby decreasing the absorption and serum levels of tetracyclines, including demeclocycline, minocycline, and tetracycline (273). However, in human research, doxycycline lacked an interaction with zinc (662; 663). Similarly, quinolones (e.g., ciprofloxacin) may also form complexes with zinc in the gastrointestinal tract and decrease the absorption of these antibiotics (274). According to secondary sources, zinc may decrease the absorption of erythromycin. However, other studies have shown that zinc may increase the efficacy of topical erythromycin. In a study comparing erythromycin with and without added zinc, the results showed a significant reduction in severity and number of acne vulgaris lesions (including inflamed lesions) in the zinc-treated group compared to those taking erythromycin alone (664). Erythromycin has been used in combination formulas with 1.2% zinc for the treatment of acne vulgaris for up to one year (115; 114). Supplementation with zinc in children with shigellosis resulted in an increase in serum shigellacidal antibodies and an increase in circulating CD20+ and CD20+CD38+ cells (257). Zinc has been shown to increase the antienterobacterial activity of Hemidesmus indicus root in vitro (665). Zinc may aid in adjunctive therapy with leprosy treatments (666). In a systematic review, zinc supplementation resulted in a significant reduction in the number of days of oral antibiotics; effects on the duration of intravenous antibiotic therapy was lacking (352).

Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In humans, zinc demonstrated an effect on platelet aggregation (232). In an in vitro study, zinc inhibited and reversed platelet-activating factor-induced aggregation, and similar inhibitory effects of zinc were observed on serotonin release (233).

AntidepressantsAntidepressants: In human research, supplementation with zinc increased the efficacy of imipramine in treatment-resistant patients (739).

Anti-inflammatoriesAnti-inflammatories: In human research, zinc has been shown to decrease C-reactive protein, lipid peroxidation, and inflammatory cytokines, and increase anti-inflammatory proteins A20 and peroxisome proliferator-activated receptor-alpha in elderly patients and in hemodialysis patients (6; 677). Additionally, in human research, zinc acexamate has been shown to be effective and well tolerated for the prevention of NSAID-induced gastroduodenal damage in patients with rheumatic disease (368). Zinc supplementation, with or without other micronutrients (unspecified), in children at risk for zinc deficiency, increased the lymphocyte ratios of CD4(+) to CD8(+) and of CD4(+)CD45RA(+) to CD4(+)CD45RO(+), increased the generation of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), decreased the generation of interleukin-10 (IL-10), and increased plasma interleukin-1 receptor antagonist (sIL-1ra) and soluble tumor necrosis factor receptor-1 (sTNF-R1) (245). Zinc supplementation increased the percentage of phagocytic blood polymorphonuclear cells and the mean phagocytic activity in patients with inflammatory rheumatic disease (678).

Antilipemic agentsAntilipemic agents: Zinc had mixed effects on lipid levels in human research. In individuals with low baseline cholesterol levels, zinc resulted in increased total and LDL cholesterol levels and lacked and effect on HDL cholesterol levels (377). In human research, zinc lacked effects on total cholesterol levels, decreased LDL cholesterol, and had mixed effects on HDL cholsterol types, with increased HDL2 and a slight decrease in HDL3 (378). In a separate clinical trial, zinc decreased total cholesterol and lacked effects on triglycerides (171; 379). According to a review, at nontoxic lower levels but still above the RDA (from close to the RDA up to 100-300mg), reported adverse effects included an increased LDL:HDL cholesterol ratio (134), and reduced HDL:total cholesterol ratios were shown in other clinical trials (135). According to reviews, long-term, high-dose administration of zinc may result in decreased HDL cholesterol levels (1). Reduced levels of HDL cholesterol were observed in other clinical trials (137; 138; 136). The mixed effect of zinc on these parameters may be due to dosing, the age and/or sex of the participant, or baseline zinc and/or plasma lipid levels (379). In animal research, cholestyramine, a bile acid sequestrant, decreased urinary zinc excretion (679). In in vitro research, treatment with HMG-CoA reductase inhibitors resulted in an active zinc signal in peripheral blood mononuclear cells (PBMCs) from low-grade atherosclerotic patients (680).

Anti-malarialsAnti-malarials: Results are contradictory for the effect of zinc on malaria symptoms (557; 554; 556; 555).

AntineoplasticsAntineoplastics: In human research, patients with head and neck cancers receiving radiotherapy had a better clinical outcome following zinc supplementation compared to those who received placebo (681; 682). Limited benefits were associated with the use of zinc for dysgeusia induced by cancer therapies (340). In human research, cisplatin was shown to increase urinary zinc excretion and reduce plasma zinc levels (276). Zinc increased the cytotoxicity of cisplatin when in the presence of the chelate ethylenediaminetetraacetic acid (EDTA), compared to cisplatin treatment alone (296). Zinc has been studied as an adjunctive therapy to leukemia medication, and side effects have been lacking, other than a slight decrease in granulocyte count (241). In vitro, zinc has been shown to induce apoptosis or inhibit the growth of cancer cells (683; 684).

AntioxidantsAntioxidants: Zinc, alone or in combination with other agents, was purported to have antioxidant effects in human and laboratory research studies (742; 743; 744; 745; 740; 746; 6; 747; 748; 9). Zinc and iron supplementation has been shown to improve zinc-related antioxidant indicators that had been impaired by iron supplementation (749).

AntiparasiticsAntiparasitics: Evidence is mixed with respect to the effect of zinc on parasitic infections in human research (150; 148; 487; 486; 561; 685).

AntiretroviralsAntiretrovirals: In human research, zinc offered benefit for some symptoms of HIV, including potentially reducing opportunistic infection and affecting the immune system (261; 190; 259; 260).

AnticonvulsantsAnticonvulsants: In human research, valproate treatment was associated with a reduction in erthryocyte, but not plasma or urinary, levels of zinc (277). The clinical significance of reduced manganese and zinc levels in treated epileptic patients was the topic of discussion (667). Valproate, birth defects, and zinc have also been the topic of discussion (668). Further details are lacking for these two publications.

BromelainBromelain: According to secondary sources, zinc may inhibit the enzymatic activity of bromelain.

CaffeineCaffeine: According to secondary sources, caffeine may decrease zinc concentrations.

Calcium saltsCalcium salts: A decrease in zinc absorption following calcium supplementation has been observed (20); increased calcium levels were observed in children following zinc supplementation (691). Calcium plus minerals, including zinc, was found to decrease bone loss in human research (750). In human research, dietary calcium lacked an effect on zinc absorption in women (751).

Chelation therapyChelation therapy: According to a systematic review, zinc therapy may result in hypersensitivity to chelation therapy (136). In human research, high doses of EDTA have been shown to increase zinc excretion; symptoms of depletion have been observed (300; 301).

ChromiumChromium: According to animal research, chromium and zinc may compete for the same transport site in the intestine and theoretically may interfere with each one's absorption (302).

Citric acidCitric acid: According to secondary sources, citric acid may complex with zinc.

Cognitive agentsCognitive agents: In human research, zinc was of limited usefulness for improving cognition in adolescent girls, and potentially in lead-exposed schoolchildren, although not all available studies agree (497; 693; 499). In adults, zinc had beneficial effects on cognitive function (208). In human research, zinc lacked effects on the psychological functioning of adults with senile dementia (154).

CopperCopper: In human research, zinc interfered with copper metabolism in some studies (317; 222; 318; 319; 242; 320; 321; 322). According to reviews and clinical trials, reported adverse effects included copper reduction with related anemia and neutropenia (134; 197; 198; 1; 222). However, some studies lacked a report of an effect of zinc supplementation on plasma copper levels (753; 754; 165; 512). Hepatic and urinary copper were reduced in patients with Wilson's disease (323). In a systematic review, the studies found that zinc therapy reduced 24-hour urinary copper excretion from 89-223mcg/dL at baseline to 73-116mgc/dL after 1-3 years of treatment (136). Non-ceruloplasmin-bound serum copper decreased on average as well, from 19.1-32mcg/dL at baseline to 14.7-15mcg/dL after treatment. In the case of studies on asymptomatic Wilson's participants, non-ceruloplasmin-bound serum copper remained below 20-25mcg/dL. Liver copper concentrations were highly variable in participants following zinc treatment but remained elevated when reported (normal range, copper in liver (dry weight): 25-50mcg/dL). One study evaluated copper balance, with all participants showing negative copper balances (-20 to -440mcg/d) within 8-13 days of initiating zinc therapy.

Dermatological agentsDermatological agents: In human research, zinc sulfate supplements given to burn victims increased healing in patients whose coefficient units of burned surface (UBS) is greater than 180 (175). In human research, patients with cutaneous leishmaniasis were injected with zinc sulfate intralesionally or took zinc orally and benefits were noted in some studies (150; 148; 487; 486). In human research, a shampoo containing 1% zinc pyrithione reduced dandruff and (PAS)-positive microorganisms on the scalp (467), and a zinc shampoo was found effective for tinea versicolor (484; 485). Zinc has also shown benefit for diaper rash (501) and incision wound healing (383; 384; 386). Dermatological effects of zinc have been shown in other human research in terms of sebum excretion (701; 702; 703; 704) and reduced symptoms related to nickel exposure (413).

DiureticsDiuretics: It has been suggested that in humans, thiazide diuretics (e.g., hydrochlorothiazide) and thiazide-like diuretics (e.g., chlorthalidone) may increase the urinary excretion of zinc (287; 288; 289; 290). Loop diuretics (e.g., furosemide) have been shown to reduce zinc concentrations and increase zinc excretion to a lesser extent than thiazide diuretics (287). However, in human research, the potassium-sparing diuretic amiloride (Midamor®) was also shown to reduce urinary zinc excretion (292). In other research, administration of diuretics lacked an effect on serum zinc levels (705).

Folic acidFolic acid: In human research, folic acid supplementation was suggested as interfering with intestinal absorption of zinc (303; 304). However, in other human and animal research, impairment was lacking (756).

Hormonal agentsHormonal agents: In human research, estrogens have been shown to reduce zinc excretion (716; 717) and plasma zinc levels (308); however, effects on plasma zinc levels were lacking in some studies (718; 719). In human research, zinc increased serum testosterone and dihydrotestosterone levels in most, but not all, studies, while effects on LH, FSH, and prolactin were lacking in most, but not all, studies (436; 391; 709; 431; 720; 489; 390; 431; 721; 387). In further human research, hormonal effects of zinc have included increased serum insulin-like growth factor I (IGF-I) concentrations (722), and there were positive correlations with IGF binding protein-3 (IGFBP-3) levels (723). In animal research, zinc showed importance for gonadal growth and pituitary synthesis of gonadotropins (724). According to a review, although use of oral contraceptives may reduce circulating zinc levels, some tissue levels may be increased, and evidence in support of an increased zinc requirement is lacking (725).

HypoglycemicsHypoglycemics: In humans, zinc has been reported to improve glycemic control, shown by decreasing HbA1c concentration, as well as decrease fasting and postprandial blood sugar (234). In human research, zinc improved both insulin secretion and insulin sensitivity and exerted insulin-like effects (235). In human research, zinc resulted in improved glucose disappearance and glucose effectiveness in a glucose challenge (236). However, in separate human research, large-dose zinc supplementation induced an elevation of HbA1c (237).

HypotensivesHypotensives: According to human research, both captopril and enalopril increased renal zinc loss; however, captopril had the greatest effect on increased zinc excretion, and decreased plasma and erythrocyte zinc levels (275). In a patient being treated with captopril, zinc supplementation was able to reverse symptoms of zinc deficiency (676).

ImmunomodulatorsImmunomodulators: In human research, zinc offered benefit to the immune system in the elderly (238; 239; 259), hemodialysis patients (256), children or young adults (240; 241), and healthy adult males (242). In human research, zinc, with or without other nutrients, affected levels of various types of T cells and other immune cells, affected levels of various cytokines, and modulated the innate immune system (243; 244; 245; 246; 247; 248; 249; 250; 251; 252; 241; 246; 254; 253; 255; 238; 239; 256; 240; 257; 258; 259; 260; 261). Similar effects, as well as other immune modifying effects, have been shown in laboratory studies (262; 263). In another study, it was determined that zinc supplementation lacked a long-lasting effect on immune status in healthy adults (262). According to expert opinion long-term, high-dose administration of zinc may result in suppressed immunity (1). According to a review, long-term, high-dose administration of zinc may result in suppressed immunity (1; 136). Reduced immune responses (phytohemagglutinin challenge, chemotaxis) were observed in a small study in which volunteers received 300mg of zinc daily for six weeks (264).

IP-6 (phytic acid)IP-6 (phytic acid): IP-6 in foods may decrease zinc absorption (305). Theoretically, IP-6 supplements could also interfere with zinc absorption, as IP-6 chelated multivalent metal ions in the gastrointestinal tract, preventing absorption (306). However, in human research, an effect on zinc absorption was lacking by the long-term use of low-phytate corn in children (757). In human research, dietary calcium lacked an effect on phytate inhibition of zinc absorption in women (751).

Iron saltsIron salts: According to secondary sources, nonheme iron may decrease zinc absorption due to competition for a common absorption pathway in the gut. However, experts suggest that when iron and zinc are taken with food, this interaction is unlikely to occur. When taken with food, zinc absorption is facilitated by proteins in food through an alternate pathway that does not compete with iron (758; 759; 760). According to secondary sources, protein-bound heme iron (found in red meats) lacks an effect on zinc absorption. In human research, zinc has had negative effects on iron bioavailability at higher doses (11mg) (311); resulted in decreased serum iron, hemoglobin levels, and transferrin saturation (312; 313); decreased plasma ferritin and the percentage of transferrin saturation (314); and resulted in anemia or reduced iron levels (195; 136). In pregnant Peruvian women, iron supplements decreased plasma zinc levels of the mother as well as cord blood zinc levels (315), and in human research, inorganic iron and heme iron inhibited zinc absorption from a turkey test meal (316). Effects of iron on zinc levels or absorption or effects of zinc on erythrocyte incorporation of iron were lacking in further human research (761; 762; 763; 764; 765), and iron, zinc, and vitamin A have been used in combination to increase hemoglobin values most effectively in anemic women (766).

Respiratory agentsRespiratory agents: Evidence is mixed with respect to the effect of zinc on the degree of respiratory illness, as shown in meta-analyses and systematic reviews (194; 553; 669; 734; 551). Evidence is mixed with respect to the effect of zinc on pneumonia (512; 192; 215; 214; 552; 547; 735).

ResveratrolResveratrol: Zinc pectinate beads were discussed as an encapsulation method for resveratrol (768).

SeleniumSelenium: Interactions with selenium have been reported (770). Zinc and selenium may play a role in thyroid metabolism (771). In human research, concurrent deficiencies in selenium and zinc may increase the risk of squamous cell carcinoma of the esophagus (772).

Vitamin AVitamin A: Supplementation with zinc may interact with vitamin A (773; 774). Zinc supplementation has been shown to increase plasma vitamin A levels (775; 776; 773), and synergistic effects of vitamin A and zinc have been suggested (629). Zinc has been used in combination with vitamin A in various clinical trials (331; 629; 777; 674). Iron, zinc, and vitamin A have been used in combination to increase hemoglobin values most effectively in anemic women (766). In patients with acne, lower levels of retinol-binding protein were found and mean serum zinc levels were significantly lower than control, without similar effects in females (778). The effect of zinc added to multivitamin supplementation containing low-dose vitamin A on plasma retinol level has been studied in children (details are lacking) (779).

Vitamin DVitamin D: In laboratory research, vitamin D has been found to be involved in zinc absorption (780). In animal research, interactions between vitamin D3 and zinc have been reported, suggesting that the combination may stimulate bone growth and mineralization (781). In human research, calcitriol lacked effects on zinc status (782).

Wound-healing agentsWound-healing agents: Supplementation with an antioxidant mixture consisting of vitamin E, vitamin C, and zinc, in burned children, resulted in a lower time to heal (740). A dressing containing zinc, in combination with calcium and manganese, has been shown to stimulate proliferation, growth, collagen I and III synthesis, and the migration of fibroblasts (741).

GeneralGeneral: According to secondary sources, foods and beverages have been shown to decrease the uptake of zinc, thereby decreasing the levels of zinc in the plasma of healthy volunteers. For this reason, it is recommended that an oral dose of zinc should be separated from food and beverages, other than water, by at least one hour.

Dairy foodsDairy foods: In human research, concomitant use of dairy products and zinc decreased zinc absorption (309). According to animal and human research, these negative effects may be due to the casein content found in dairy products (783; 760).

FiberFiber: According to secondary sources, foods high in fiber content may interfere with the absorption of zinc.

IP-6 (phytic acid)IP-6 (phytic acid): IP-6 in foods like grains (e.g., corn), legumes, seeds (e.g., sunflower), and soy may decrease zinc absorption (305). Theoretically, IP-6 supplements could also interfere with zinc absorption, as IP-6 chelated multivalent metal ions in the gastrointestinal tract, preventing absorption (306). However, in human research, effects of long-term use of low-phytate corn were lacking on zinc absorption in children (757). According to reviews, foods high in phytic acid result in reduced zinc absorption (784; 760).

Iron-containing foodsIron-containing foods: According to secondary sources, nonheme iron may decrease zinc absorption due to competition for a common absorption pathway in the gut. However, experts suggest that when iron and zinc are taken with food, this interaction is unlikely to occur. When taken with food, zinc absorption is facilitated by proteins in food through an alternate pathway that does not compete with iron (758; 759; 760). According to secondary sources, protein-bound heme iron (found in red meats) lacks an effect on zinc absorption. In human research, zinc has had negative effects on iron bioavailability at higher doses (11mg) (311); resulted in decreased serum iron, hemoglobin levels, and transferrin saturation (312; 313); decreased plasma ferritin and the percentage of transferrin saturation (314); and resulted in anemia or reduced iron levels (195; 136). In pregnant Peruvian women, iron supplements decreased plasma zinc levels of the mother as well as cord blood zinc levels (315), and in human research, inorganic iron and heme iron inhibited zinc absorption from a turkey test meal (316). Effects of iron on zinc levels or absorption or effects of zinc on erythrocyte incorporation of iron were lacking in further human research (761; 762; 763; 764; 765), and iron, zinc, and vitamin A have been used in combination to increase hemoglobin values most effectively in anemic women (766).

Leafy green vegetablesLeafy green vegetables: In in vitro research, it was shown that some green leafy vegetables contained high levels of zinc (785).

Multiple micronutrient powdersMultiple micronutrient powders: In human research, home fortification of foods with multiple micronutrient powders, including at least iron, zinc, and vitamin A, improved iron status in children under two years of age (786).

PhosphorusPhosphorus: According to secondary sources, phosphorus may interfere with the absorption of zinc.

ProteinProtein: In late-middle-aged men, supplementation with zinc lacked an effect on whole-body protein metabolism or synthesis rates of albumin and fibrinogen (787). In human research, the absorption of zinc from soy protein meals is reduced in some situations; the reduction depends on the degree of replacement, the phytic acid and zinc content of the food, and the meal protein content (788). In human research, zinc absorption was inhibited by some (bovine serum albumin and dephytinized soyabean-protein isolate), but not all, protein sources (789).

SugarSugar: In human research, high consumption of sugar resulted in a decrease in zinc status in children and teenagers (310).

Zinc-fortified foodsZinc-fortified foods: According to a systematic review, both zinc intake and absorption were increased when zinc-fortified foods were consumed (118).

CopperCopper: In human research, zinc interfered with copper metabolism in some studies (317; 222; 318; 319; 242; 320; 321; 322). According to reviews and clinical trials, reported adverse effects included copper reduction with related anemia and neutropenia (134; 197; 198; 1; 222). However, some studies lacked a report of an effect of zinc supplementation on plasma copper levels (753; 754; 165; 512). Hepatic and urinary copper were reduced in patients with Wilson's disease (323). In a systematic review, the studies found that zinc therapy reduced 24-hour urinary copper excretion from 89-223mcg/dL at baseline to 73-116mgc/dL after 1-3 years of treatment (136). Non-ceruloplasmin-bound serum copper decreased on average as well, from 19.1-32mcg/dL at baseline to 14.7-15mcg/dL after treatment. In the case of studies on asymptomatic Wilson's participants, non-ceruloplasmin-bound serum copper remained below 20-25mcg/dL. Liver copper concentrations were highly variable in participants following zinc treatment but remained elevated when reported (normal range, copper in liver (dry weight): 25-50mcg/dL). One study evaluated copper balance, with all participants showing negative copper balances (-20 to -440mcg/d) within 8-13 days of initiating zinc therapy.

CytokinesCytokines: Zinc supplementation, with or without other micronutrients (unspecified), in children at risk for zinc deficiency, increased the generation of IL-2 and IFN-gamma, decreased the generation of IL-10, and increased plasma sIL-1ra and soluble tumor necrosis factor receptor-1 (sTNF-R1) (245). In vitro, zinc supplementation increased interferon-gamma release and impaired IL-10 release (262). An increase in IL-4 and a decrease in TNF-alpha was shown in another clinical trial (244). In human research, zinc lacked effects on nasal IL-8 levels (347). Zinc lacked an effect on cytokine levels in some human studies (348).

Iron statusIron status: In human research, zinc supplementation in children lacked an effect on hemoglobin concentrations (792). Zinc use decreased serum hemoglobin in pregnant women (313). In human research, zinc has had negative effects on iron bioavailability at higher doses (11mg) (311); resulted in decreased serum iron, hemoglobin levels, and transferrin saturation (312; 313); decreased plasma ferritin and the percentage of transferrin saturation (314); and resulted in anemia or reduced iron levels (195; 136). Effects of iron on zinc levels or absorption or effects of zinc on erythrocyte incorporation of iron were lacking in further human research (761; 762; 763; 764; 765), and iron, zinc, and vitamin A have been used in combination to increase hemoglobin values most effectively in anemic women (766)

Lipid profileLipid profile: Zinc had mixed effects on lipid levels in human research. In individuals with low baseline cholesterol levels, zinc resulted in increased total and LDL cholesterol levels and lacked an effect on HDL cholesterol levels (377). In human research, zinc lacked effects on total cholesterol levels, decreased LDL cholesterol, and had mixed effects on HDL cholsterol types, with increased HDL2 and a slight decrease in HDL3 (378). In a separate clinical trial, zinc decreased total cholesterol and lacked effects on triglycerides (171; 379). According to a review, at nontoxic lower levels but still above the RDA (from close to the RDA up to 100-300mg), reported adverse effects included an increased LDL:HDL cholesterol ratio (134), and reduced HDL:total cholesterol ratios were shown in other clinical trials (135). According to reviews, long-term, high-dose administration of zinc may result in decreased HDL cholesterol levels (1). Reduced levels of HDL cholesterol were observed in other clinical trials (137; 138; 136). The mixed effect of zinc on these parameters may be due to dosing, the age and/or sex of the participant, or baseline zinc and/or plasma lipid levels (379). In animal research, cholestyramine, a bile acid sequestrant, decreased urinary zinc excretion (679). In in vitro research, treatment with HMG-CoA reductase inhibitors resulted in an active zinc signal in peripheral blood mononuclear cells (PBMCs) from low-grade atherosclerotic patients (680).

Skin sebumSkin sebum: An inhibitory effect of zinc on lipase of three propionibacterium species in human pilosebaceous follicles and a small decrease in fatty acid content of surface lipids in skin sebum have been reported in vivo (701). In clinical research, a lotion containing 1.2% zinc and 4% erythromycin applied to the forehead twice daily for three months was shown to significantly reduce sebum excretion rate (SER) after three weeks (702). In healthy males, zinc sulfate supplementation (440mg daily for three weeks) has been shown to significantly decrease mean skin sebum secretion rates compared to control (p<0.28) (703). However, in patients with a lower normal range (< 1.0mg/L), serum zinc concentration who were hospitalized for chronic leg ulcers, three daily doses of 220mg of zinc sulfate was shown to increase sebum secretion, an effect that was more marked in males and which the authors speculated may be due to a zinc-induced rise in plasma testosterone (704).

Vitamin AVitamin A: Zinc supplementation has been shown to increase plasma vitamin A levels (775; 776; 773). The effect of zinc added to multivitamin supplementation containing low-dose vitamin A on plasma retinol level has been studied in children (details are lacking) (779).

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.